A spontaneous non-human primate demyelinating disease, Japanese Macaque Encephalomyelitis (JME), has recently been described.^1–5 JME bears marked clinical and pathological similarities to multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO). To date, JME is the only known naturally-occuring MS-like disease in non-human primates. Here, we describe topography of gadolinium based contrast agent (GBCA) enhancing lesions typical in JME, presented in a lesion distribution probability map based on 21 cases of acute JME. This represents an important step in not only understanding this disease, but also in making meaningful comparisons to human demyelinating diseases.Twenty-one animals experiencing an acute episode of JME were identified and selected for MRI examination. All MRI data were acquired on a whole-body Siemens 3 Tesla (T) MRI instrument (Erlangen, Germany) using a quadrature radiofrequency (RF) coil with inner diameter of 15 cm. Animals were initially sedated with Telazol, intubated and maintained on 1% isoflurane in 100% O₂ and were continuously monitored by pulse oximetry, respiration, and end tidal CO₂ levels during the study. Quantitative R₁ (≡1/T₁) mapping was performed with a multiple-inversion recovery experiment employing 3D T₁-weighted magnetic prepared rapid acquisition gradient echo (MPRAGE) sequence (TR: 2500 ms; TE: 3.49 ms; FA: 8°; FOV 130 mm x 97.5 mm x 96 mm, matrix: 192x144x96; TI: 200, 900, 2000ms, no inversion). R₁ maps were acquired before and 6 minutes after bolus injection of 0.2mmol (gadoteridol)/kg GBCA). Difference maps were created (=R_1post-CA – R_1pre-CA) and used to manually identify lesions. Only acute (defined as GBCA-enhancing) lesions were considered in this analysis. R₁ maps from 6 healthy Japanese macaques were nonlinearly coregistered and then averaged to create a common reference space for analysis. Lesion masks were created manually for each JME case based on the R₁ difference maps; R₁ maps were coregistered to the reference image, and lesion masks were transformed accordingly. Binarized lesion masks in the reference space were then summed to create the final lesion distribution probability map shown in Figure 1.A total of 100 GBCA-enhancing white matter lesions were identified in 21 Japanese macaques (median 4 lesions/animal, range 2-11) presenting with clinical symptoms typical of JME: ataxia, paresis, or optic involvement. The median age was 2 years [range 0.3-26 years] and 43% were female. Animals most commonly presented with lesions in the cerebellum (including peduncles, CBLL; n=18; 86% of animals), followed by the brainstem (n=11; 52%), internal capsule (IC; n=8; 38%), and upper cervical spinal cord (SC; n=5; 24%), as demonstrated in Figure 2. Overall lesion load across the population was greatest in the cerebellum (n=55 lesions), followed by the IC (n=14), brainstem (n=11), and SC (n=7). Lesions were also identified in the corpus callosum (CC), cerebral white matter (CWM), and periventricular white matter (PVWM). CBLL lesions were most frequent near the midline. Lesions were often observed bilaterally within cases, and demonstrated equal bilateral probability across all animals studied.Lesion morphology and distribution are important in obtaining correct differential diagnosis in demyelinating disease.⁶ This work describes GBCA-enhancing lesion distribution typical of JME, a novel spontaneous demyelinating disease in non-human primates. Brainstem and SC lesions are found medially, suggesting a transverse myelitis as seen in ADEM and NMO, and laterally as seen in MS. CWM lesions are often sub- or juxtacortical; making distinctions between PVWM and CWM can be challenging due small brain size and close proximity of structures. Indeed, a juxtacortical WM lesion could be simultaneously classified as periventricular. However, these are both typical of MS, so the absolute distinction here may be of limited importance. Lack of optical tract involvement or longitudinally extensive transverse myelitis in this cohort suggests dissimilarity to NMO.⁷ Based on GBCA enhancing lesion distribution alone, JME appears most similar to MS or ADEM. Additionally, pediatric MS patients often have higher infratentorial lesion load and are more capable of completely resolving acute lesions compared to adult MS.⁸ High infratentorial lesion load found in JME, and the ability for near complete acute lesion resolution in some cases⁵ suggests JME may be more similar to pediatric than adult MS. JME commonly occurs in animals prior to sexual maturity (72% of this cohort). Image coregistration across the population was imperfect, so this map serves primarily for illustrative purposes rather than precise quantification. Additional characterization of disease natural history, T₂ lesion distribution, and CSF assays will be necessary before confident comparisons can be made with human disease. JME is a novel and promising non-human primate model of inflammatory and demyelinating disease with potential applications in understanding MS and MS-like diseases.